Quick lock connector for connecting a capillary to a fluidic conduit of a fluidic component

ABSTRACT

A fitting ( 200 ) for providing a fluid connection between a capillary ( 202 ) and a fluidic conduit ( 204 ) of a fluidic component ( 230 ), wherein the fitting ( 200 ) comprises a capillary reception configured for receiving the capillary ( 202 ), a force applicator ( 206 ) configured for being operable to apply a fixing force for fixing the capillary ( 202 ) within the fitting ( 200 ), a force limitation mechanism ( 208 ) configured for limiting the fixing force being applicable by the force applicator ( 206 ) to the capillary ( 202 ), a force splitter ( 210, 234 ) configured for splitting the fixing force into an advance force component for advancing the capillary ( 202 ) received in the capillary reception towards the fluidic component ( 230 ) and into a clamping force component for clamping the capillary ( 202 ) received in the capillary reception within the fitting ( 200 ), and a biasing mechanism ( 212 ) particularly arranged between the force applicator ( 206 ) and the force splitter ( 210, 234 ) and configured for biasing the force splitter ( 210, 234 ) against the capillary ( 202 ).

BACKGROUND ART

The present invention relates to fluidically coupling fluidiccomponents, in particular in a high performance liquid chromatographyapplication.

In liquid chromatography, a fluidic sample (mobile phase) may be pumpedthrough conduits and a column comprising a material (stationary phase)which is capable of separating different components of the fluidicanalyte. Such a material, so-called beads which may comprise silica gel,may be filled into a column tube which may be connected to otherelements (like a sampling unit, a flow cell, containers including sampleand/or buffers) by conduits.

The flow path of the mobile phase typically comprises plural individualcomponents coupled together, which, in turn, might also be comprised ofindividual sub-components. Due to the high pressure applied in most HPLCapplication, pressure sealing of the components in and along the flowpath is required. Further, in case of requirement of biocompatibility,it has to be ensured that all surfaces of components (includingconduits) along the flow path, which may come in contact with the mobilephase and the sample fluid, are comprised of materials generallyconsidered as being biocompatible, i.e. not to release ions (e.g. frommetal parts) which may contaminate the sample and/or a column packagingmaterial, and/or adversely affect the analysis itself. Accordingly,proper sealing is required to ensure such biocompatibility. Sealingsshould also provide for a small dead volume and low carryover.

A so called fitting is a fluidic component being capable of providing asealed connection between a capillary and another fluidic conduit (suchas another capillary or a channel in a substrate or the like).

U.S. Pat. No. 3,973,792 discloses that, in a connecting device forconnecting chromatographic separating columns of glass to terminalfittings on a chromatographic apparatus, each end of the column issurrounded by a metallic sleeve. A sleeve made of synthetic plasticmaterial, which is of substantially stable shape at least up to atemperature of 350° centigrade even if subjected to pressure, isinterposed between said end and said metallic sleeve. The plastic sleevehas at least one conical end face and is held in sealing engagement withthe end of the separating column, on one hand, and with the metallicsleeve, on the other hand, by a sleeve shaped thrust member, which isaxially movable relative to the metallic sleeve to exert an axial forceon said plastic sleeve. A radial sealing force is exerted on thesynthetic plastic sleeve through its conical end face by an abuttingcomplementary conical surface. Connecting means for gas-tightly anddetachably connecting the ends of the column to the terminal fittings ofthe apparatus are provided on the metallic sleeve.

WO 92/15426 discloses an apparatus and a method for connecting the endof a tubular body, particularly a chromatographic capillary tube, to adetection or injection device fitting. WO 92/15426 provides an apparatuswhich comprises a holder having a ferrule for holding the tubular body.Connection of the tubular body to a device fitting is aided by aninsertion assembly. The insertion assembly is adapted to contain theholder and force the ferrule into a seated relation with the device.

However, the requirements regarding sealing performance and mechanicalstability of a fluidic component of fluidic measurement devicesincreases with further increasing operation pressure values. At the sametime, fast and easy handling of such a fitting by a user is required.

DISCLOSURE

It is an object of the invention to provide an efficient sealing fluidiccomponent for a fluidic device which is simple in operation. The objectis solved by the independent claims. Further embodiments are shown bythe dependent claims.

According to an exemplary embodiment of the present invention, a fittingfor providing a fluid connection between a capillary and a fluidicconduit (such as a further capillary, a fluidic channel in a substrate,etc.) of a fluidic component is provided, wherein the fitting comprisesa capillary reception configured for receiving the capillary, a forceapplicator configured for being operable (particularly by a user) toapply a fixing force for fixing the capillary within the fitting, aforce limitation mechanism configured for limiting the fixing forcebeing applicable by the force applicator to the capillary, a forcesplitter configured for splitting the fixing force into an advance forcecomponent (particularly oriented longitudinally along an extensiondirection of the capillary reception) for advancing the capillaryreceived in the capillary reception (particularly forwardly) towards thefluidic component and into a clamping force component for (particularlycircumferentially and/or inwardly) clamping the capillary received inthe capillary reception within the fitting, and a biasing mechanism(particularly arranged between the force applicator and the forcesplitter) configured (particularly mounted within the fitting) forbiasing the force splitter against the capillary.

According to another exemplary embodiment, a fluidic device forconducting a fluidic sample is provided, wherein the fluidic devicecomprises a fluidic component having a fluidic conduit, a capillary, anda fitting having the above mentioned features for providing a fluidconnection between the capillary and the fluidic conduit for conductingthe fluidic sample through the fluidic device.

According to still another exemplary embodiment, a method of fluidicallycoupling a capillary with a fluidic conduit of a fluidic component by afitting is provided, wherein the method comprises receiving thecapillary in a capillary reception of the fitting, operating a forceapplicator of the fitting to apply a fixing force for fixing thecapillary within the fitting, limiting the fixing force being applicableby the force applicator to the capillary by a force limitation mechanismof the fitting, splitting the fixing force, by a force splitter of thefitting, into an advance force component for advancing the capillaryreceived in the capillary reception towards the fluidic component andinto a clamping force component for clamping the capillary received inthe capillary reception within the fitting, and biasing the forcesplitter against the capillary by a biasing mechanism of the fitting,the biasing mechanism being particularly arranged between the forceapplicator and the force splitter.

In an embodiment, a fluidic fitting is provided which is configured forcoupling a capillary with another fluidic conduit by applying a failureresistant mechanism, operable by a user, for fixing the capillary at thefitting, while at the same time applying a reproducible and predefinedfixing force to the capillary. This fixing force can be renderedsufficiently large so as to securely fasten the capillary at thefitting, at the same time a force limitation mechanism prevents anexceeding fixing force which would deteriorate or even destroy thefitting or the capillary. Moreover, a biasing mechanism such as a springor a spring package may bias the force splitter to apply a certainpressure to the capillary. In a scenario in which, due to temperature oraging effects, the force applied from the force applicator to thecapillary becomes too small, the biasing mechanism ensures that in eachconfiguration a sufficient biasing force for sealingly connecting thecapillary within the fitting is provided.

In the following, further embodiments of the fitting will be explained.However, these embodiments also apply to the fluidic device and themethod.

In an embodiment, the force applicator has a lever operable by a userand an eccentric shaft rigidly coupled to the lever so that pivoting ofthe lever (starting from an operation mode in which the capillary is ina non-fixed state in the capillary reception) pushes the eccentric shafttowards (i.e. in direction of) the biasing mechanism to thereby applythe fixing force (finishing at an operation mode in which a capillary isin a fixed state in the capillary reception). By providing a levermechanism it is easy for a user to manually operate the forceapplicator, since it is sufficient to pivot the lever using the muscleforce of the user only to fix the capillary to the fitting.

The force applicator may have a rod like configuration when the leverforms one end of the rod. An opposing end of this rod may be formed byan eccentric shaft, i.e. a shaft around which a pivoting is possible.The eccentric shaft may be mounted in a housing of the fitting.Therefore, rotation of the eccentric shaft triggered by actuating thelever will automatically result in a continuous increase of the forceapplied towards the capillary, since the thicker end of the eccentricshaft may be pressed increasingly powerful in direction of the biasingmechanism. Hence, the biasing mechanism will transmit a correspondingapplied fixing force, merely exerted by pivoting the lever, towards theforce splitter.

The skilled person will understand that a lever mechanism is only onepossibility for a user operated component suitable for applying thefixing force. As an alternative to the lever based force applicator(with the defined abutment mechanism) it is possible to use a screw inconnection with a latch. Still other embodiments may embody the forceapplicator by a differential thread. Also a hydraulic or a pneumaticforce applicator is possible. It is also possible to embody the forceapplicator by a screw nut in combination with a wrench.

In an embodiment, the force applicator is configured to be manuallyoperable by a user, particularly is configured to be toollessly operableby a user. Such an embodiment has the advantage that no tools orautomatic drive mechanism such as a motor is necessary for operating,particularly activating, the capillary fixation. In contrast to this,with a small amount of muscle force only it is possible to reliably fixthe capillary to the fitting.

In an embodiment, the force limitation mechanism has a first abutmentmember forming part of the force applicator and has a second abutmentmember forming part of a fitting housing. The first abutment member andthe second abutment member may be configured so as to abut to oneanother upon exceeding a predefined degree of actuating the forceapplicator (for instance upon exceeding a certain rotation angle of alever) for inhibiting continued operation of the force applicator (whichwould result in a fixing force exceeding a predefined maximum fixingforce) thereby inhibiting or preventing exceeding of the fixing force.When no force is applied to a capillary, i.e. when the force applicatoris in an inactive (or non-force applying) state, the first abutmentsection does not contact the second abutment section. However, uponactuating the force applicator, for instance by rotating a lever of alever-based force applicator, the first abutment section will becontacted with the second abutment section at a certain point of timeduring the lever operation. This will have the effect that a furtherrotation of the lever will not result in a further increased fixingforce. Therefore, by a simple mechanical abutment mechanism, it ispossible to define a maximum fixing force acting on the capillary. It isnot possible that this force is exceeded, since this is prevented by theabutment of the first abutment section against the second abutmentsection.

In an embodiment, the force splitter comprises a collet at leastpartially circumferentially surrounding at least a part of thecapillary. The force splitter may further comprise a first ferrule beingbiased against the collet by the biasing mechanism, wherein the colletand the first ferrule are shaped at mutually abutting surfaces forsplitting the fixing force into the advance force component and theclamping force component. Hence, the collet and the first ferrule mayhave surfaces being slanted with regard to an extension direction of thecapillary reception (and particularly may be slanted relative to oneanother, particularly with slightly different slanting angles furtherimproving the force transmission between the collet and the firstferrule), so that, in view of this simple geometric shaping, thetransmitted force will be divided into two vector components. Onecomponent will compress the capillary radially and thereby fix it withinthe fitting, whereas the other component will drive or bias thecapillary forwardly (i.e. in direction to the fluidic conduit of thefluidic component) so that an end surface of the capillary will abut orwill be pushed against a cooperating sealing surface of the fluidicconduit or the fluidic component, thereby providing for a fluid tightsealing.

In an embodiment, the above mentioned first ferrule is an annular diskwith a tapering through hole. The central through hole may receive thecapillary and may have an internal through hole diameter whichcontinuously increases towards a free end of the capillary. Therefore,the force splitting may be efficiently performed by the first ferrule inconjunction with the collet.

In an embodiment, the collet is a (for instance slitted) tube with atleast one tapering end section. Slitting a tube with one or morecircumferential slits extending parallel to a central axis of thecapillary reception allows to provide a structure which can becompressed efficiently, for instance crimped or plastically deformed inanother way, upon applying a circumferential compression force to thecollet. The external surface of the tubular collet may have anotherdiameter which, at least over a part of the extension of the collet,continuously increases from the end of the collet opposing the fluidiccomponent to be connected towards the other end of the collet facing thefluidic component to be connected. Therefore, the force splitting may beefficiently performed by the first ferrule in conjunction with thecollet.

In an embodiment, the biasing mechanism is a spring assembly,particularly an assembly of a plurality of plate washers (other types ofsprings are possible, for instance coil springs or leaf springs). Forinstance, eight plate washers may be combined, wherein pairs of adjacentplate washers are aligned in parallel to one another with continuouscontact surfaces there between. A pair of convex spring washers may befollowed by a pair of concave spring washers, and so on, so that asequence of spring washer pairs of alternating (or opposite) curvatureis obtained. Such a plate washer arrangement has the advantage ofproviding a net force basically in a forward direction, i.e. in anextension direction of the capillary reception. The number of used platewashers as well as the spring constant connected thereto may be selectedin accordance with a specific application.

In an embodiment, the fitting further comprises a coupling piece,particularly a coupling disk, arranged between a pivotable eccentricshaft of the force applicator and the biasing mechanism and having acurved coupling surface coupled to the eccentric shaft and a planarcoupling surface coupled to the biasing mechanism. Such a coupling piecemay be a basically disk-shaped member with a front face which may have asurface perpendicular to an extension of the capillary, whereas a backsurface thereof may be curved (particularly in a concave way). Hence,when the eccentric shaft pivots as a result of a user actuation, theeccentric shaft rolls up on the curved surface of the coupling body witha low friction so as to efficiently transfer the actuation force withlow losses onto the spring assembly.

In an embodiment, the fitting further comprises a two-piece fittinghousing (or a fitting housing having more than two separate pieces)having a first housing piece and a second housing piece, wherein thefirst housing piece is rotatable relative to the second housing piecewhen the force applicator is operated to not apply the fixing force, andwherein the first housing piece is fixed relative to the second housingpiece when the force applicator is operated to apply the fixing force.With such a two-part housing, it is possible that a user firstly fixesthe fluidic component to be coupled with the capillary on the rotatablehousing piece, for instance by rotating one of the housing pieces forperforming a screwing connection between the fluidic component and oneof the housing pieces. Due to the mutually movable adaptation of the twohousing pieces relative to one another this fastening procedure is notdisturbed by the other housing piece. Upon activating the fixing forceby operating the force applicator by a user, the second housing piecemay be immobilized relative to the first housing piece, therebyachieving a stable and reproducible configuration.

In an embodiment, the force applicator is pivotably mounted on the firsthousing piece. More specifically, a pivoting axis of the forceapplicator may be oriented perpendicular to a rotation direction of thefirst housing piece relative to the second housing piece.

In an embodiment, the second housing piece has a connection sectionconfigured for being connected to a cooperating connection section ofthe fluidic component. In such a configuration, the second housing piecemay for instance form a male part of a connection system, wherein thefluidic component hereby forms the female part. In other words, a frontend of the second housing piece may be a protrusion, whereas a back endof the fluidic component may be a recess. However, in anotherembodiment, this functionality may be inverted. Thus, the second housingpiece may alternatively form a female part of a connection system,wherein the fluidic component hereby forms the male part.

In an embodiment, the fitting further comprises a tapering secondferrule at a front end of the fitting and being configured for providinga sealed coupling to the fluidic component. Such a second ferrule may bebasically cone shaped with an internal through hole for providing fluidcommunication from the capillary towards the fluidic conduit to beconnected. Hence, the second ferrule may conically taper towards a frontend of the fitting, so that a tip thereof may be inserted into a recessof the fluidic component to be connected. Such a second ferrule may bemade of a plastic material such as PEEK (Polyetheretherketone) which canbe deformed upon application of pressure, thereby providing for a highperformance sealing surface even under high pressure conditions (such asin case of modern liquid chromatography applications with pressurevalues of 1000 bar and more).

In an alternative embodiment, the fitting further comprises a fluidicplanar structure reception gap for clampingly receiving a fluidic planarstructure as the fluidic component having integrated therein the fluidicconduit. In such an alternative embodiment, an insertion gap may beformed between the two opposing ends of the fitting. Such a gap isconfigured to insert a fluidic planar structure (which may also bedenoted as a fluidic chip) therein for providing a fluid communicationbetween the capillary and an internal fluidic conduit within the fluidicplanar structure. The skilled person is aware of the fact that, forinstance for liquid chromatography applications, a plurality of layersmay be laminated to one another, which layers have been processedbeforehand so that an internal fluidic conduit can be formed within thisplanar or chip-like arrangement. In the present embodiment, the fluidiccoupling between such a fluidic conduit of the fluidic planar structureand the capillary may be achieved by a clamping or pressing force whichis applied between the fitting and the fluidic planar structure uponactuating the force applicator or force enhancer.

In an embodiment, the fluidic planar structure reception gap isconfigured for receiving the fluidic planar structure upon inserting thefluidic planar structure along an insertion direction into the gap,which insertion direction may be perpendicular to an extension of thecapillary reception. Hence, it is for instance possible that the fluidicplanar structure is inserted along a basically vertical insertiondirection, whereas an extension of the capillary reception may bebasically horizontal. This may ensure for a precise and reliable highpressure connection of the capillary with a fluidic conduit of theplanar chip.

In the following, further embodiments of the fluidic device will beexplained. However, these embodiments also apply to the fitting and themethod.

Fluidic devices according to exemplary embodiments may be particularlysuitable for use as fluidic connection pieces for connecting parts of afluidic instrument such as a liquid chromatographic system or the like.For example, columns, fractioners, detectors, or the like, of a liquidchromatography apparatus may be connected as fluidic components of sucha fluidic device.

In an embodiment, at least the part of the capillary being received inthe capillary reception is at least partially circumferentially coveredby a sleeve. Such a tubular sleeve may locally thicken the capillary andmay be made of a metallic structure which is pressed onto the capillary,for instance by crimping, so that it covers the entire perimeter of thecapillary.

In an embodiment, the fluidic component is a fluidic planar structurewhich comprises a plurality of laminated sheets being patterned so as toform the fluidic conduit for conducting the fluidic sample integrated inthe layer sequence. Thus, the fitting may provide a connection between aconventional capillary system and a planar fluidic chip device which mayhave a chromatographic column integrated therein.

In an embodiment, the fluidic component is a processing elementconfigured for processing the fluidic sample. Thus, such a processingelement may process the fluid, for instance separate it, purify it,apply a tempering step, or the like.

Particularly, the processing element may be a chromatographic separationcolumn which may separate different fractions of a fluidic sample due toa different affinity of the various fluidic fractions to a stationaryphase of the separation column. For instance, by applying a gradientrun, the trapped fractions may be released from the separation columnindividually, thereby separating them.

The fluidic device may comprise a processing element filled with aseparating material. Such a separating material which may also bedenoted as a stationary phase may be any material which allows anadjustable degree of interaction with a sample so as to be capable ofseparating different components of such a sample. The separatingmaterial may be a liquid chromatography column filling material orpacking material comprising at least one of the group consisting ofpolystyrene, zeolite, polyvinylalcohol, polytetrafluorethylene, glass,polymeric powder, silicon dioxide, and silica gel, or any of above withchemically modified (coated, capped etc) surface. However, any packingmaterial can be used which has material properties allowing an analytepassing through this material to be separated into different components,for instance due to different kinds of interactions or affinitiesbetween the packing material and fractions of the analyte.

At least a part of the processing element may be filled with a fluidseparating material, wherein the fluid separating material may comprisebeads having a size in the range of essentially 1 μm to essentially 50μm. Thus, these beads may be small particles which may be filled insidethe separation section of the microfluidic device. The beads may havepores having a size in the range of essentially 0.01 μm to essentially0.2 μm. The fluidic sample may be passed through the pores, wherein aninteraction may occur between the fluidic sample and the pores.

The fluidic device may be configured as a fluid separation system forseparating components of the sample. When a mobile phase including afluidic sample passes through the fluidic device, for instance with ahigh pressure, the interaction between a filling of the column and thefluidic sample may allow for separating different components of thesample, as performed in a liquid chromatography device.

However, the fluidic device may also be configured as a fluidpurification system for purifying the fluidic sample. By spatiallyseparating different fractions of the fluidic sample, a multi-componentsample may be purified, for instance a protein solution. When a proteinsolution has been prepared in a biochemical lab, it may still comprise aplurality of components. If, for instance, only a single protein of thismulti-component liquid is of interest, the sample may be forced to passthe columns. Due to the different interaction of the different proteinfractions with the filling of the column (for instance using a gelelectrophoresis device or a liquid chromatography device), the differentsamples may be distinguished, and one sample or band of material may beselectively isolated as a purified sample.

The fluidic device may be configured to analyze at least one physical,chemical and/or biological parameter of at least one component of themobile phase. The term “physical parameter” may particularly denote asize or a temperature of the fluid. The term “chemical parameter” mayparticularly denote a concentration of a fraction of the analyte, anaffinity parameter, or the like. The term “biological parameter” mayparticularly denote a concentration of a protein, a gene or the like ina biochemical solution, a biological activity of a component, etc.

The fluidic device may be implemented in different technicalenvironments, like a sensor device, a test device, a device forchemical, biological and/or pharmaceutical analysis, a capillaryelectrophoresis device, a liquid chromatography device, a gaschromatography device, an electronic measurement device, or a massspectroscopy device. Particularly, the fluidic device may be a HighPerformance Liquid device (HPLC) device by which different fractions ofan analyte may be separated, examined and analyzed.

The fluidic device may be configured to conduct the mobile phase throughthe system with a high pressure, particularly of at least 600 bar, moreparticularly of at least 1200 bar (for instance up to 2000 bar).

The fluidic device may be configured as a microfluidic device. The term“microfluidic device” may particularly denote a fluidic device asdescribed herein which allows to convey fluid through microchannelshaving a dimension in the order of magnitude of less than 500 μm,particularly less than 200 μm, more particularly less than 100 μm orless than 50 μm or less (for instance down to 15 μm or 12 μm). Theanalysis system may also be configured as a nanofluidic device. The term“nanofluidic device” may particularly denote a fluidic device asdescribed herein which allows to convey fluid through nanochannels witha flow rate of less than 100 nl/min, particularly of less than 10nl/min.

BRIEF DESCRIPTION OF DRAWINGS

Other objects and many of the attendant advantages of embodiments of thepresent invention will be readily appreciated and become betterunderstood by reference to the following more detailed description ofembodiments in connection with the accompanied drawings. Features thatare substantially or functionally equal or similar will be referred toby the same reference signs.

FIG. 1 shows a liquid separation device in accordance with embodimentsof the present invention, particularly used in high performance liquidchromatography (HPLC).

FIG. 2 illustrates a fitting for providing a fluid connection between acapillary and a fluidic conduit of a separation column according to anexemplary embodiment of the invention.

FIG. 3 shows a spring packet implemented in the fitting of FIG. 2.

FIG. 4 illustrates the geometry of a force transmission along ahorizontal direction of FIG. 2.

FIG. 5 shows an exploded view of a fitting according to an exemplaryembodiment of the invention.

FIG. 6 shows the fitting of FIG. 5 in an assembled cross-sectional view.

FIG. 7 illustrates a fitting for providing a fluid connection between acapillary and a fluidic conduit of a planar chip device according to anexemplary embodiment of the invention.

The illustration in the drawing is schematically.

Referring now in greater detail to the drawings, FIG. 1 depicts ageneral schematic of a liquid separation system 10. A pump 20 receives amobile phase from a solvent supply 25, typically via a degasser 27,which degases and thus reduces the amount of dissolved gases in themobile phase. The pump 20—as a mobile phase drive—drives the mobilephase through a separating device 30 (such as a chromatographic column)comprising a stationary phase. A sampling unit 40 can be providedbetween the pump 20 and the separating device 30 in order to subject oradd (often referred to as sample introduction) a sample fluid into themobile phase. The stationary phase of the separating device 30 isconfigured for separating compounds of the sample liquid. A detector 50is provided for detecting separated compounds of the sample fluid. Afractionating unit 60 can be provided for outputting separated compoundsof sample fluid.

While the mobile phase can be comprised of one solvent only, it may alsobe mixed from plural solvents. Such mixing might be a low pressuremixing and provided upstream of the pump 20, so that the pump 20 alreadyreceives and pumps the mixed solvents as the mobile phase.Alternatively, the pump 20 might be comprised of plural individualpumping units, with plural of the pumping units each receiving andpumping a different solvent or mixture, so that the mixing of the mobilephase (as received by the separating device 30) occurs at high pressureand downstream of the pump 20 (or as part thereof). The composition(mixture) of the mobile phase may be kept constant over time, the socalled isocratic mode, or varied over time, the so called gradient mode.

A data processing unit 70, which can be a conventional PC orworkstation, might be coupled (as indicated by the dotted arrows) to oneor more of the devices in the liquid separation system 10 in order toreceive information and/or control operation. For example, the dataprocessing unit 70 might control operation of the pump 20 (e.g. settingcontrol parameters) and receive therefrom information regarding theactual working conditions (such as output pressure, flow rate, etc. atan outlet of the pump). The data processing unit 70 might also controloperation of the solvent supply 25 (e.g. setting the solvent/s orsolvent mixture to be supplied) and/or the degasser 27 (e.g. settingcontrol parameters such as vacuum level) and might receive therefrominformation regarding the actual working conditions (such as solventcomposition supplied over time, flow rate, vacuum level, etc.). The dataprocessing unit 70 might further control operation of the sampling unit40 (e.g. controlling sample injection or synchronization sampleinjection with operating conditions of the pump 20). The separatingdevice 30 might also be controlled by the data processing unit 70 (e.g.selecting a specific flow path or column, setting operation temperature,etc.), and send—in return—information (e.g. operating conditions) to thedata processing unit 70. Accordingly, the detector 50 might becontrolled by the data processing unit 70 (e.g. with respect to spectralor wavelength settings, setting time constants, start/stop dataacquisition), and send information (e.g. about the detected samplecompounds) to the data processing unit 70. The data processing unit 70might also control operation of the fractionating unit 60 (e.g. inconjunction with data received from the detector 50) and provides databack.

From the example of FIG. 1, it can be seen that the flow path of themobile phase typically comprises plural individual components, such aspump 20, separating device 30, sampling unit 40, and detector 50, whichare coupled together and which might also be comprised of individualsub-components. Also, fluid conduits, e.g. capillaries, for conductingthe fluid are provided as indicated by the solid connections in FIG. 1.Coupling of parts, components and fluid conduits, in particular whenusing exchangeable or modular parts, is usually provided by usingfittings.

For transporting liquid within the liquid separation system 10,typically tubings (e.g. tubular capillaries) are used as conduits forconducting the liquid. Fittings are commonly used to couple pluraltubings with each other or for coupling a fluid conduit (e.g. a tubing)to any device. For example, fittings can be used to connect respectivefluid conduit to an inlet and an outlet of the chromatographic column 30in a liquid-sealed fashion. Any of the components in the fluid path(solid line) in FIG. 1 may be connected by fluid conduits e.g. usingfittings. While the fluid path after the column 30 is usually at lowerpressure, e.g. 50 bar or below, the fluid path from the pump 20 to theinlet of the column 30 is under high pressure, currently up to 1200 bar,thus posing high requirements to fluid tight connections.

Due to the high pressure applied in most HPLC applications, pressuresealing of the components in and along the flow path is required.Further, in case of requirement of biocompatibility, it has to beensured that all surfaces of components (including conduits) along theflow path, which may come in contact with the mobile phase and thesample fluid, are comprised of materials generally considered as beingbiocompatible, i.e. not releasing ions (e.g. from metal parts) which maycontaminate the sample and/or a column packaging material, and/oradversely affect the analysis itself. Accordingly, proper sealing isrequired to ensure such biocompatibility.

FIG. 2 illustrates a fitting 200 for providing a fluid connectionbetween a capillary 202 and a fluidic conduit 204 (only indicatedpartially and schematically in FIG. 2) of a fluidic component 230according to an exemplary embodiment of the invention.

The fitting 200 can be used for multiple purposes, but particularly forproviding a high pressure sealing connection between the capillary 202(having an internal fluid conducting lumen) on the one hand and acapillary or the like forming the fluidic conduit 204 of the fluidiccomponent 230 on the other hand. The fluidic component 230 can be achromatographic separation column, as the one denoted with referencenumeral 30 in FIG. 1.

In the following, the construction of the fitting 200 will be explainedin more detail. The fitting 200 comprises a housing which is constitutedof different housing parts, such as those denoted with referencenumerals 222 and 224 in FIG. 2. The housing has, as an interior recessthereof, a capillary reception volume which is shaped and dimensioned asa central basically cylindrical recess and which is configured forreceiving and accommodating the capillary 202. The capillary 202 has aportion which is shown in FIG. 2 outside of the fitting 200 and whichmay be free of any further cover layers. However, another section of thecapillary 202 being accommodated within the fitting 200 can besurrounded by an optional metallic sleeve 232. The capillary 202,covered by the sleeve 232 along a subsection thereof, can be inserted bya user in the capillary reception by a sliding motion along a horizontaldirection of FIG. 2 from a left hand side to a right hand side.

A force applicator 206, in the shown embodiment also acting as a forceenhancer, is provided and configured for being operable to apply afixing force for fixing the capillary 202 received within the capillaryreception volume of the fitting 200. Hence, by operating the forceapplicator 206 by a user, the capillary 202 may be clamped in thecapillary reception so that it cannot be removed from the fitting 200 inthe clamped state.

Beyond this, a force limitation mechanism 208 is provided and configuredfor limiting the fixing force amplitude of the fixing force which isapplicable by the force applicator 206 to the capillary 202. In otherwords, the force limitation mechanism 208, as described below in moredetail, ensures that the fixing force applied to the capillary 202 willnever exceed a predefined maximum fixing force. Thus, the capillary 202may be prevented from any deterioration due to a too high force actingthereon.

Moreover, a force splitter 210, 234 is a mechanism which is configuredfor splitting the fixing force into two components. The first componentis an advance force component which has the tendency of advancing thecapillary 202 received in the capillary reception forwardly towards thefirst component, i.e. towards a right hand side of FIG. 2. A secondcomponent of the applied fixing force split by the force splitter 210,234, is a clamping force component which clamps the capillary 202received in the capillary reception within the fitting 200. Thisclamping force is directed circumferentially inwardly, i.e. is appliedtowards a full circumference of the capillary 202.

Furthermore, a biasing mechanism 212 is provided. As can be taken fromFIG. 2, the biasing mechanism 212 is an assembly of eight plate washers240, i.e. four concave plate washers and four convex plate washers,which are arranged in a pairwise alternating way so as to form thespring package shown in FIG. 2. The biasing mechanism 212 is arrangedbetween the force applicator 206 and the force splitter 210, 234 (butmay be located elsewhere). It may be configured for biasing a forcedsplitter 210, 234 against the capillary. In other words, a biasing forcemay be applied from the biasing mechanism which promotes a forwardmotion of the capillary 202, i.e. towards the fluidic conduit 204 to beconnected thereto. This ensures a proper sealing at an interface betweencapillary 202 and fluidic conduit 204. Furthermore, in case of areduction or loss of a forward pressing force which presses thecapillary 202 against the fluidic conduit 204, for example due to ageingeffects or temperature induced effects, the biasing mechanism maydeliver an additional force which maintains the sealed coupling betweenfluidic component 230 and capillary 202. Furthermore, this additionallypromotes a clamping of the capillary 202 within the fitting 200 so thatthe biasing mechanism can also prevent an undesired sliding of thecapillary 202 within the fitting 200.

As can be taken from FIG. 2, the force applicator 206 has a lever 214which is manually operable by a user. For this purpose, the lever 214 isanatomically shaped to be grippable by a hand of the human being. Theforce applicator 206 furthermore has an eccentric shaft 216 having ashaft axis which is arranged perpendicular to the paper plane of FIG. 2.Eccentric shaft 216 is rigidly coupled to the lever 214, i.e. isintegrally formed therewith from a metallic material or the like, sothat pivoting the lever 214 pushes the eccentric shaft 216 towardsbiasing mechanism 212 to thereby apply the fixing force. Due to theeccentric mounting of the force applicator 206 at the casing or housingof the fitting 200, a rotation of the lever 214 in a direction asindicated by an arrow 270 in FIG. 2 also results in a rotation of theeccentric shaft 216, as indicated by an arrow 272. Due to the eccentricassembly, the force applied by the eccentric shaft 216 forwardly, i.e.towards the right hand side end of the capillary 202, is continuouslyincreased with increasing pivoting angle. Since the lever 214 ismanually operable by a user without the need of using a specific tool,handling of the fitting 200 is very user convenient.

As mentioned above, pivoting the lever 214 continuously increases thefixing force applied from the force applicator 206 onto the capillary200, transmitted by various intermediate components as described belowin more detail. However, the fitting 200 has a mechanism of preventingthat the applied force exceeds a maximum value which is adjusted so thatthe application of the force does not deteriorate the capillary 202. Forthis purpose, the force limitation mechanism has a first abutment member218 which is a surface portion of the force applicator 206 whichapproaches a corresponding second abutment member 220 of the housing 222(a surface thereof) with continued rotation of the force applicator 206.Hence, the second abutment member 220 forms part of the fitting housing222. More precisely, the second abutment member 220 is a surface portionof a corresponding housing part 222 which projects or protrudes so as tobe selectably brought in contact with the first abutment member 218 whenthe lever 214 has been rotated until it comes in contact with thehousing part 222. This abutment inhibits a further continued operationof the force applicator 206, thereby inhibiting exceeding of the fixingforce. When the abutment members 218, 220 abut against one another,further continued rotation of the lever 240 along arrow 270 is renderedimpossible, thereby disabling a further increase of the fixing force.

The above mentioned force splitter mechanism 210, 234 is realized in theshown embodiment of the fitting 200 particular by the cooperation of twocomponents: collet 234 and first ferrule 210. The collet 234circumferentially surrounds the entire capillary 202. The first ferrule210 is biased against the collet 234 by a biasing force exerted bybiasing mechanism 212. The collet 234 and the first ferrule 210 areshaped to have corresponding abutting surfaces 238. These are slantedrelative to an extension direction of the capillary 202 (the extensiondirection is a horizontal direction according to FIG. 2) for splittingthe fixing force into the longitudinal advance force component and thecircumferential and inwardly directed clamping force component. Thefirst ferrule 210 is configured as an annular disk with a taperingthrough hole. The through hole of the first ferrule 210 has an innerdiameter at an interface to the biasing element 210 which is smallerthan an inner diameter of the first ferrule 210 at an interface facingthe fluidic component 230. In view of the described geometry, the forceapplied by the force applicator 206 is divided into two vectorcomponents, one compressing the capillary 202 and the other one pressingor pushing the capillary 202 towards the right hand side of FIG. 2.

As can be taken from FIG. 2, the collet 234 may be configured as alongitudinally slitted tube with a tapering end section (the one on theleft hand side of FIG. 2). In other words, the end section of the collet234 contacting the first ferrule 210 is slanted as well, to ensure aproper force transmission. To match the tapering of the first ferrule210, the end section of the collet 234 increases its diameter from theleft hand side of FIG. 2 to the right hand side of FIG. 2. The slantingangles of the collet 234 and of the first ferrule 210 may be the same ormay be slightly different (for instance may differ by an angle in arange between 1° and 10°), wherein a slight difference in the slantingangle may improve the force transmission between the collet 234 and thefirst ferrule 210.

A coupling piece 242 is arranged as a separate member between thepivotable eccentric shaft 216 of the force applicator 206 on the onehand and the biasing mechanism 212 on the other hand. The coupling piece242 has a concavely curved coupling surface 244 contacting andcooperating with the eccentric shaft 216. Opposing to the curvedcoupling surface 244, the coupling piece 242 has a planar couplingsurface 246 which contacts and cooperates with the biasing mechanism212. The coupling piece 242 is also embodied as an annular member, i.e.a basically cylindrical member with an internal through hole. Uponpivoting the lever 214, an external cylindrical surface of the eccentricshaft 216 performs a rolling motion on the concave curved surface 244 ofthe coupling piece 242.

FIG. 2 furthermore shows that the above mentioned housing is constitutedas a multiple piece housing having a first housing piece 222 and asecond housing piece 224. The first housing piece 222 is rotatablerelative to the second housing piece 224 in the absence of a fixingforce applied by the force applicator 206. In other words, in anoperation mode as shown in FIG. 2 in which no fixing force is applied tothe force applicator 206 towards a capillary 202, the first housingpiece 222 can be rotated relative to the second housing piece 224, forinstance by holding one of the housing pieces 222, 224 and pivoting downon one 224 or 222. Moreover, the first housing piece 222 is fixedrelative to the second housing piece 224 when the force applicator 206is operated to apply the fixing force. Thus, the pivoting of the forceapplicator 206 not only applies a fixing force of the capillary 200 butalso ensures to selectively immobilize or mobilize the housing pieces222, 224 relative to one another.

It is possible to provide a connection element 296 (mounted in thehousing pieces 222, 224) of the fitting 200 with an external thread 226.The latter may be configured for being connectable to a cooperatinginternal thread 228 of the fluidic component 230. Therefore, the fluidiccomponent 230 may be connected to the fitting 200 by screwing, i.e. byrotating the second housing piece 224 relative to the fluidic component230, wherein the first housing piece 222 can be disabled from followingthis rotation when the force applicator 206 is not in its fixed but inits released state. Therefore, it is advantageous for a describedscrewing connection that the two housing pieces 222, 224 are rotatablerelative to one another.

After this screwing operation, rotation of the pivoting lever 214 notonly fixes the capillary 200 in a sealed way within the cavity receptionof the fitting 200, but simultaneously disables undesired rotationbetween housing parts 222, 224.

An arrow-shaped tapering second ferrule 248 is provided as a furtherpart of the fitting 200. It is arranged in a front end of the fitting200 and is configured for providing a sealed coupling to the fluidiccomponent 230. The tapering second ferrule 248 is shaped, in the shownembodiment, as a hollow cone-like member of a material (such as PEEK orany other appropriate plastic material) which deforms upon applyingpressure, thereby contributing significantly to the sealing betweenfitting 200 and fluidic component 230.

For operating the fitting 200, a screwing connection between thecooperating threads 226, 228 may be formed. A user may guide thecapillary 202 through the capillary reception of the fitting 200 untilit abuts through the fluidic conduit 204 to which it is to befluidically connected. Subsequently, the lever 214 may be pivoted as toapply the fixing force exerted onto the capillary 202 in a forward and acircumferential direction as well. Simultaneously, this pivotingdisables rotation between housing parts 222, 224.

The capillary 202 may be made of a flexible material (for instance aplastic material or a metallic material such as steel). For example, anouter diameter d of the capillary 202 may be 1.6 mm. The sleeve 232(which can also be denoted as a socket) may be slid onto the capillary202 and may be welded to the capillary 202, for instance by laserwelding. The biasing mechanism 212 is an active member for providing asealing force independently of temperature effects or aging effects. Theplate washers 240 of the biasing mechanism 212 can be made of steelwhich may be harder than capillary steel. Housing part 224 may be aknurl sleeve being freely rotatable when the lever 214 is in the openstate of FIG. 2. When the lever is closed (not shown) the knurl sleeveis fixed at the housing part 222. The first ferrule 210 compresses thecollet 234 so that the capillary 202 can be clamped in placecircumferentially. The force applicator 206 and the coupling piece 242may be made of the same material, for instance steel. With the shownforce application mechanism, a muscle force of 30 N may be enough toobtain a holding force or fixing force of 800 N. An overload protectionpreventing a too high force to be applied to the capillary 202 isprovided by the force limitation mechanism 208 and also by the springpacket 212.

The force transmission is performed from the lever 214 to the pressuredisk or coupling piece 242, from the coupling piece 242 to the springpacket 212, and from the spring packet 212 to the back ferrule 210. Dueto the corresponding shaping of back ferrule 210 and the slitted collet234, the back ferrule 210 presses the collet 234 inwardly. At the sametime, the back ferrule 210 presses the collet 234 forwardly, i.e.towards the direction of the front ferrule 248.

In the following, several advantageous properties of the fitting 200according to an exemplary embodiment of the invention are summarized:The fitting 200 is high pressure-resistant up to 2,000 bar whichcorresponds to 400 N sealing force at a 25 μm capillary. Compensation ofthe pressure and temperature fluctuations caused by springs 240 isperformed. A force amplifier function is fulfilled by an eccentric levermechanism. Hence, a manual force of only about 25 N is sufficient. It ispossible to orient the lever 214 by decoupling. The fitting 200 has anoverload protection, is tool-free operable and is easy to use. It hasreplaceable wear parts. The fitting 200 has a long lifetime because ofits exclusively linear motion. Hence, there is no stress or torsion. Thefitting 200 is fully compatible with standard column connections. It hasa releasable connection.

An applied hand force on the lever 214 results in a clamping force of800 N (corresponds 3,600 bar pressure). This corresponds to anamplification of factor 32. The clamping force is applied to the springassembly or biasing mechanism 212, which acts as overload protection andcompensator. This spring package subsequently pushes back ferrule 210,which compresses the collet 234. Through the compressed collet 234, thecapillary 202 is kept and in addition pressed forward to the columnport. Sealing is accomplished with the ferrule 248 on PEEK base.

FIG. 3 shows the arrangement of the plate washers 240 forming thebiasing assembly 212 in detail. As can be taken from FIG. 3, the eightspring washers 240 used in this embodiment are grouped to four groups ofadjacent spring pairs, wherein concave spring pairs and convex springpairs alternate along an extension of the spring packet shown in FIG. 3.

FIG. 4 illustrates a force transmission to the back ferrule 210 and fromthere to the collet 234 (subsequently to the capillary 202). Dependingon the wedge angle β which is a design parameter when embodying afitting 200, the applied actual loading force F_(a) has a normalcomponent F_(n) and a tension force component F_(r).

FIG. 5 shows an exploded view of a fitting according to an exemplaryembodiment of the invention. The shown fitting is appropriate for theuse with capillary connection systems. Spring packet 212 serves as apressure and temperature balancing element as well as for overloadprotection. As high pressure sealing and capillary holders, a socket500, a clamping cone 248 and a tapering piece 502 are foreseen.Reference numerals 500 and 502 form collet 234. Also back ferrule 210contributes to the function of a high pressure sealing and capillaryholders.

Hollow screw or connection element 296 serves as a connector to theseparation column via a corresponding thread 226. Eccenter lever 206 isfixed to the eccentric housing part 222 by means of shaft 506. Theeccentric housing part 222 also serves as a coupling nut for theconnection element 296. Together with a pressure disk 508, a clampingforce is transmitted to the spring packet 212 and then to the backferrule 210 to be accommodated in the connection element 296. Alignmentmay be performed in an open state by pivoting the knurl sleeve orhousing part 224 while maintaining the eccentric housing part 222spatially fixed.

FIG. 6 shows the fitting of FIG. 5 in an assembled state.

FIG. 7 shows a fitting 900 according to still another exemplaryembodiment of the invention. Many of the components shown in FIG. 7 aresimilar or identical to those shown in FIG. 2. However, the differencesbetween FIG. 2 and FIG. 7 will be described in the following in moredetail.

A main difference between the embodiment of FIG. 7 and the embodiment ofFIG. 2 is that with the embodiment of FIG. 7, the capillary 202 is notconnected to a conventional chromatographic separation column 230, butin contrast with this with a fluidic channel 204 formed in a fluidicplanar structure 904 which is made from a number of thin sheets 930 (ofplastic or metal) laminated together and processed so as to haveinternal grooves. In combination, the grooves form fluidic channel 204.For mounting the fluidic planar structure 904, the fitting 900 has afluidic planar structure reception cap 902 which is configured forclampingly receiving the fluidic planar structure 904 as a fluidiccomponent having integrated therein the fluidic conduit 204 and to befluidically coupled to the capillary 202. The fluidic planar structurereception gap 902 is configured for receiving the fluidic planarstructure 904 when the latter is longitudinally shifted along aninsertion direction 906 which is perpendicular to an extension directionof the capillary 202 and the capillary reception.

A counter piece housing part 908 is provided as well which presses froma right hand side against the fluidic planar structure 904 when beinginserted in the fluidic planar structure reception gap 902. A plunger910 presses the chip 904 towards an opposing surface of the housingpiece 224. The plunger 910 is biased to a left hand side via a spring912 mounted between the plunger 910 and the counter piece housing 908.

In operation, the fluidic planar structure 904 is inserted in thefluidic planar structure reception cap 902. It will then be pressed bythe biasing force of the spring 912 and by means of the plunger 910towards the left hand side of the fluidic planar structure reception gap902, i.e. will sealingly abut on the surface of the housing piece 224.Upon pivoting the lever 214 after having inserted the capillary 202 intoa capillary reception, the capillary 202 is fixed within the fitting 900and will at the same time be sealingly forced to abut to an end of thefluidic channel 204 integrated in the multilayer laminated microfluidicplanar structure 904.

It should be noted that the term “comprising” does not exclude otherelements or features and the “a” or “an” does not exclude a plurality.Also elements described in association with different embodiments may becombined. It should also be noted that reference signs in the claimsshall not be construed as limiting the scope of the claims.

1. A fitting for providing a fluid connection between a capillary and afluidic conduit of a fluidic component, the fitting comprising: acapillary reception configured for receiving the capillary; a forceapplicator configured for being operable to apply a fixing force forfixing the capillary within the fitting; a force limitation mechanismconfigured for limiting the fixing force being applicable by the forceapplicator to the capillary; a force splitter configured for splittingthe fixing force into an advance force component for advancing thecapillary received in the capillary reception towards the fluidiccomponent and into a clamping force component for clamping the capillaryreceived in the capillary reception within the fitting; a biasingmechanism, particularly arranged between the force applicator and theforce splitter, and configured for biasing the force splitter againstthe capillary.
 2. The fitting according to the claim 1, wherein theforce applicator has a lever operable by a user.
 3. The fittingaccording to the claim 2, wherein the lever comprises an eccentric shaftrigidly coupled to the lever so that pivoting the lever pushes theeccentric shaft towards the biasing mechanism to thereby apply thefixing force.
 4. The fitting according to claim 1, wherein the forcelimitation mechanism has a first abutment member forming part of theforce applicator and has a second abutment member forming part of afitting housing, wherein the first abutment member and the secondabutment member are configured so as to abut to one another forinhibiting continued operation of the force applicator therebyinhibiting exceeding of the fixing force.
 5. The fitting according toclaim 1, wherein the force splitter comprises a collet at leastpartially circumferentially surrounding at least a part of the capillaryand comprises a first ferrule being biased against the collet by thebiasing mechanism, wherein the collet and the first ferrule are shapedat mutual abutting surfaces, particularly are slanted relative to anextension direction of the capillary, for splitting the fixing forceinto the advance force component and the clamping force component. 6.The fitting according to claim 5, wherein the first ferrule is anannular disk with a tapering through hole.
 7. The fitting according toclaim 5, wherein the collet is a tube, particularly a slitted tube, moreparticularly a longitudinally slitted tube, with a tapering end section.8. The fitting according to any claim 1, wherein the biasing mechanismis a spring assembly, particularly an assembly of a plurality of platewashers, more particularly an assembly of one or more concave platewashers and one or more convex plate washers.
 9. The fitting accordingto claim 1, further comprising a coupling piece arranged between apivotable eccentric shaft of the force applicator and the biasingmechanism and having a curved coupling surface coupled to the eccentricshaft and a planar coupling surface coupled to the biasing mechanism.10. The fitting according to claim 1, further comprising a fittinghousing, particularly a two-piece fitting housing, having a firsthousing piece and a second housing piece, wherein the first housingpiece is rotatable relative to the second housing piece in the absenceof a fixing force applied by the force applicator, and wherein the firsthousing piece is fixed relative to the second housing piece when theforce applicator is operated to apply the fixing force.
 11. The fittingaccording to claim 10, wherein the second housing piece. has aconnection section, particularly an external screw, configured for beingconnected to a cooperating connection section, particularly an internalscrew, of the fluidic component.
 12. The fitting according to claim 1,further comprising a fluidic planar structure reception gap configuredfor clampingly receiving a fluidic planar structure as the fluidiccomponent having integrated therein the fluidic conduit.
 13. The fittingaccording to claim 12, wherein the fluidic planar structure receptiongap is configured for receiving the fluidic planar structure in aninsertion direction which is perpendicular to an extension direction ofthe capillary reception.
 14. A fluidic device for conducting a fluidicsample, the fluidic device comprising a fluidic component having afluidic conduit; a capillary; and a fitting according to claim 1 forproviding a fluid connection between the capillary when received in thefitting and the fluidic conduit of the fluidic component when connectedto the fitting for conducting the fluidic sample through the fluidicdevice.
 15. A method of fluidically coupling a capillary with a fluidicconduit of a fluidic component by a fitting, the method comprising:receiving the capillary in a capillary reception of the fitting;operating a force applicator of the fitting to apply a fixing force forfixing the capillary within the fitting; limiting the fixing force beingapplicable by the force applicator to the capillary by a forcelimitation mechanism of the fitting; splitting the fixing force, by aforce splitter of the fitting, into an advance force component foradvancing the capillary received in the capillary reception towards thefluidic component and into a clamping force component for clamping thecapillary received in the capillary reception within the fitting;biasing the force splitter against the capillary by a biasing mechanismof the fitting, the biasing mechanism being particularly arrangedbetween the force applicator and the force splitter. 16-29. (canceled)